Interpretive Summary: Flavonoids are abundant in plant foods and products derived from them, e.g., fruits, vegetables, tea, and red wine, and in many observational studies their intake is inversely associated with the risk of chronic diseases, e.g., certain cancers, cardiovascular disease, and neurodegenerative disorders. While absorption, metabolism, and actions of flavonoids have been partly defined, these results reveal a marked inter-individual variation, likely due to a combination of environmental, physiological, epigenetic, and genetic factors. Since flavonoids are subject to extensive metabolism via detoxification mechanism in our body, in this study, we examined the effect of parental exposure to a diet high in saturated fats and fructose 1 month before conception through lactation, on liver metabolism of the flavonoid quercetin in both parent and offspring rats. Parental rats were fed a diet containing 9.9% coconut fat, 0.5% cholesterol, 30% fructose, and 30% glucose or a control diet containing 11% corn oil and 60% glucose. After weaning, offspring were fed the control diet for an additional 12 weeks. Hepatic metabolism capacity toward quercetin was then determined in parental and offspring rats. We found that high dietary fructose and saturated fat decreased liver metabolic capacity toward quercetin in female rats and in utero exposure to the diet decreased the capacity of their pups.

Technical Abstract:
Objective
Phase II biotransformation of flavonoids generates bioactive metabolites in vivo. However, data on the effect of environmental and physiological factors and fetal programming on phase II pathways toward flavonoids are limited. We examined the effect of parental exposure to a diet high in saturated fats and fructose 1 mo before conception through lactation on in vitro hepatic UDP-glucuronosyltransferase (UGT) activity toward quercetin in both parent (F0) and offspring (F1) rats, as well as the interaction between diet and sex.
Methods
Parents were fed a diet containing 9.9% coconut fat, 0.5% cholesterol, 30% fructose, and 30% glucose (SFF) or a control (C) diet containing 11% corn oil and 60% glucose. After weaning, offspring were fed the C diet for an additional 12 wk. Glucuronidation rate of microsomal UGT was determined with 30 µM quercetin and 12.5 µg protein in a total volume of 100 µL after a 15-min incubation at 37°C. Three quercetin glucuronides (7-OH, 3’-OH, and 4’-OH) were quantified.
Results
In the F0 females, the SFF diet decreased by 29 and 19% the production rate of 3’- and 4’-OH quercetin glucuronides, respectively, as compared to the C diet (P =0.05). Production rate of 7-OH quercetin glucuronide in the female F1 rats born to C dams was 59% larger than in their male counterparts (P <0.05) but no difference was observed in the offspring of SFF dams.
Conclusion
High dietary fructose and saturated fat decreased UGT capacity toward quercetin in female rats and in utero exposure to the diet decreased the glucuronidation capacity of their pups.